2-200490214-AGGCGCGGT-A

Position:

• chr2-200490214-AGGCGCGGT-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_152387.4(KCTD18):​c.1159_1166delACCGCGCC​(p.Thr387fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,614,106 control chromosomes in the GnomAD database, including 126 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0078 (9 hom., cov: 33)
  • Exomes 𝑓: 0.011 (117 hom.)
• Consequence: KCTD18 NM_152387.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.40

Genes affected

KCTD18 (HGNC:26446): (potassium channel tetramerization domain containing 18) Predicted to be involved in protein homooligomerization. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 2-200490214-AGGCGCGGT-A is Benign according to our data. Variant chr2-200490214-AGGCGCGGT-A is described in ClinVar as [Benign]. Clinvar id is 776345.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD18	NM_152387.4	c.1159_1166delACCGCGCC	p.Thr387fs	frameshift_variant	7/7	ENST00000359878.8	NP_689600.2
KCTD18	NM_001321547.2	c.1159_1166delACCGCGCC	p.Thr387fs	frameshift_variant	7/7		NP_001308476.1
KCTD18	NM_001321548.2	c.532_539delACCGCGCC	p.Thr178fs	frameshift_variant	7/7		NP_001308477.1
KCTD18	NM_001321550.2	c.532_539delACCGCGCC	p.Thr178fs	frameshift_variant	7/7		NP_001308479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD18	ENST00000359878.8	c.1159_1166delACCGCGCC	p.Thr387fs	frameshift_variant	7/7	1	NM_152387.4	ENSP00000352941.3
KCTD18	ENST00000409157.5	c.1159_1166delACCGCGCC	p.Thr387fs	frameshift_variant	7/7	1		ENSP00000386751.1

Frequencies

GnomAD3 genomes AF: 0.00776 AC: 1182 AN: 152248 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.00224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00981

Gnomad ASJ AF: 0.0427

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00868 AC: 2181 AN: 251372 Hom.: 14 AF XY: 0.00862 AC XY: 1171 AN XY: 135880

Gnomad AFR exome AF: 0.00222

Gnomad AMR exome AF: 0.00752

Gnomad ASJ exome AF: 0.0424

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00170

Gnomad FIN exome AF: 0.00125

Gnomad NFE exome AF: 0.0114

Gnomad OTH exome AF: 0.0137

GnomAD4 exome AF: 0.0108 AC: 15849 AN: 1461740 Hom.: 117 AF XY: 0.0107 AC XY: 7751 AN XY: 727154

Gnomad4 AFR exome AF: 0.00197

Gnomad4 AMR exome AF: 0.00847

Gnomad4 ASJ exome AF: 0.0392

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00221

Gnomad4 FIN exome AF: 0.00152

Gnomad4 NFE exome AF: 0.0120

Gnomad4 OTH exome AF: 0.0111

GnomAD4 genome AF: 0.00776 AC: 1182 AN: 152366 Hom.: 9 Cov.: 33 AF XY: 0.00734 AC XY: 547 AN XY: 74508

Gnomad4 AFR AF: 0.00224

Gnomad4 AMR AF: 0.00980

Gnomad4 ASJ AF: 0.0427

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.0108

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0122 Hom.: 0

Bravo AF: 0.00835

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0140

EpiControl AF: 0.0127

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs565245989; hg19: chr2-201354937;